Anti-Human Transferrin Receptor Antibody Permeating Blood-Brain Barrier

A fusion protein comprising the amino acid sequences of a humanized anti-human transferrin receptor antibody and iduronate 2-sulfatase,

• wherein the amino acid sequence of iduronate 2-sulfatase is linked to the light chain of the antibody on the C-terminal side or the N-terminal side of the light chain, or linked to the heavy chain of the antibody on the C-terminal side or the N-terminal side of the heavy chain, and
• wherein the light chain variable region and the heavy chain variable region of the antibody are selected from (1) or (2) below:
• (1) the light chain variable region comprising the amino acid sequence having an identity not lower than 90% to the amino acid sequence set forth as SEQ ID NO:
• 191, and comprising the amino acid sequence set forth as SEQ ID NO:16 as CDR1, the amino acid sequence set forth as SEQ ID NO:18 as CDR2, and the amino acid sequence set forth as SEQ ID NO:20 as CDR3, and
• the heavy chain variable region comprising the amino acid sequence having an identity not lower than 90% to the amino acid sequence set forth as SEQ ID NO:
• 205, and comprising the amino acid sequence set forth as SEQ ID NO:88 as CDR1, the amino acid sequence set forth as SEQ ID NO:90 as CDR2, and the amino acid sequence set forth as SEQ ID NO:92 as CDR3;
• (2) the light chain variable region comprising the amino acid sequence having an identity not lower than 90% to the amino acid sequence set forth as SEQ ID NO:
• 191, and comprising the amino acid sequence set forth as SEQ ID NO:16 as CDR1, the amino acid sequence set forth as SEQ ID NO:18 as CDR2, and the amino acid sequence set forth as SEQ ID NO:20 as CDR3, and
• the heavy chain variable region comprising the amino acid sequence having an identity not lower than 90% to the amino acid sequence set forth as SEQ ID NO:
• 205, and comprising the amino acid sequence set forth as SEQ ID NO:89 as CDR1, the amino acid sequence set forth as SEQ ID NO:90 as CDR2, and the amino acid sequence set forth as SEQ ID NO:92 as CDR3.

A fusion protein comprising the amino acid sequences of a humanized anti-human transferrin receptor antibody and iduronate 2-sulfatase, wherein the amino acid sequence of the antibody is selected from the group consisting of (1) to (4) below:

• (1) the light chain variable region of the antibody comprises the amino acid sequence set forth as SEQ ID NO:191, and the heavy chain variable region of the antibody comprises the amino acid sequence set forth as SEQ ID NO:205;
• (2) the light chain variable region of the antibody comprises the amino acid sequence set forth as SEQ ID NO:193, and the heavy chain variable region of the antibody comprises the amino acid sequence set forth as SEQ ID NO:205;
• (3) the light chain variable region of the antibody comprises the amino acid sequence set forth as SEQ ID NO:194, and the heavy chain variable region of the antibody comprises the amino acid sequence set forth as SEQ ID NO:205;
• and
• (4) the light chain variable region of the antibody comprises the amino acid sequence set forth as SEQ ID NO:195, and the heavy chain variable region of the antibody comprises the amino acid sequence set forth as SEQ ID NO:205.

A fusion protein comprising the amino acid sequences of a humanized anti-human transferrin receptor antibody and iduronate 2-sulfatase, wherein the amino acid sequence of the antibody is selected from the group consisting of (1) to (8) below:

• (1) the light chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO:196, and the heavy chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO:210;
• (2) the light chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO:198, and the heavy chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO:210;
• (3) the light chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO:200, and the heavy chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO:210;
• (4) the light chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO:202, and the heavy chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO:210;
• (5) the light chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO:196, and the heavy chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO:212;
• (6) the light chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO:198, and the heavy chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO:212;
• (7) the light chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO:200, and the heavy chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO:212;
• and
• (8) the light chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO:202, and the heavy chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO:212.